Collaborative research group discovers a key pathway in the development of acute myeloid leukemia – and a potential new therapeutic strategy to treat the disease

Dr. Mingjing Xu and Ayesh Seneviratne pose in the Schimmer Lab at the University of Toronto.

Despite
progress in the treatment of acute myeloid leukemia (AML), many patients still
die from relapse or experience significant side effects from treatment. Dr.
Aaron Schimmer, who is Research Director of the Princess
Margaret Cancer Centre and co-lead of OICR’s Acute Leukemia Translational
Research Initiative, worked with his
collaborators to understand the root cause of AML relapse to develop more effective
and less toxic therapies. Their recent findings are both surprising and
promising.

The
group, which consists of researchers from across Ontario and abroad,
investigated the pathways that are uniquely important to the growth and
development of leukemic stem cells (LSCs) – also known as the cells at the
“root” of the disease. They discovered a key pathway, as described in Cell Stem Cell, which can be altered to control how LSCs mature.
Interestingly, they found that this process can be modulated with an essential
phospholipid (a type of fat), called phosphatidylserine.

“We discovered a pathway that these stem cells rely on. We investigated further and found that interfering with lipid metabolism – that is, the fats within these cells – could potentially slow their growth and reduce their ability to cause relapse,” says Ayesh Seneviratne, MD/PhD candidate in the Schimmer Lab at the University of Toronto and co-first author of the publication.

Normally, phosphatidylserine
is important in maintaining the integrity of the cell membrane and normal cell
function, but the authors found that within LSCs, phosphatidylserine acted as a
trigger for the cell to lose its self-renewal properties. They are the first
group to describe increasing phosphatidylserine as a potential therapeutic
strategy for AML.

“We now better understand
the function of this metabolite in leukemia, and in turn, we have found a new way
to target the disease,” says Dr. Mingjing Xu, postdoctoral fellow in the
Schimmer Lab and co-first author of the publication. “We are enthusiastic to
pursue further studies and unravel how phosphatidylserine ceases leukemia
growth.”

Schimmer says that this work
could not have been done without the contributions of many collaborators.

“This discovery is a product
of a concerted effort between many researchers,” says Schimmer. “Together, we’ve
found new insights into the biology of leukemia and turned those insights into
a new potential therapeutic strategy.”

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